AGING AND OXIDATION IN SKELETAL AND CARDIAC MUSCLE

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The career goals of the candidate include building an internationally recognized independent research program in the area of active calcium transport and its relationship to the aging process. At the same time the candidate is interested in becoming a Full Professor at an academic institution. The candidate is currently an Assistant Professor at a major state university which has an excellent research environment with the exception of the heavy teaching load required of its faculty. Although her laboratory has demonstrated its ability to undertake first rate research, research progress is likely to be slowed by the excessive demands of non-research related activities on the candidate's time and energy. An Independent Scientist Award (ISA) would relieve this situation by substantially reducing the candidate's teaching and service responsibilities to a minimum in order to allow her to concentrate on research activities and to foster existing and new research collaborations during this crucial time in her research career development. The ISA is expected to significantly stimulate the candidate's research productivity and hence competitiveness for future funding. The proposed research addresses the mechanism and regulation of active calcium transport in sarcoplasmic reticulum (SR) membranes in both cardiac and fast twitch skeletal muscle, and how this process is affected by aging of the organism. Major research aims include: (1) identification of oxidative modifications to the Ca-ATPase and SR lipids initiated by exposure of isolated SR vesicles to reactive oxygen species, and if these simulate any of the observed age-related changes; (2) definition of the role of the cellular environment in modifying the susceptibility of SR membranes to oxidative conditions; (3) identification of age-related modifications, and associated structural and functional alterations of the Ca-ATPase and SR lipids in muscle; and (4) identification of the physical mechanism of phospholamban's regulation of the cardiac Ca- ATPase, and how this may be altered in aging or oxidative stress. These goals will involve an integrated approach to examining biochemical function and its relation to protein structure at the primary, secondary, tertiary and quartenary level.